AB0219 LONG-TERM OUTCOMES OF METHOTREXATE IN ELDERLY-ONSET RA IMPLEMENTING THE TREAT-TO-TARGET STRATEGY
Authors: H. Baba, T. Sugihara, T. Ishizaki, M. Nomura, T. Hosoya, M. Kamiya, T. Matsumoto, K. Kubo, F. Hirano, N. Miyasaka, M. Kojima, S. Yasuda, M. Harigai
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Continuation of methotrexate (MTX) treatment is recommended in both MTX responder and non-responder elderly-onset RA (EORA) patients. However, there are insufficient data on its effectiveness and long-term safety, although we have previously reported that a treat-to-target (T2T) strategy targeting low disease activity (LDA) is safe and effective in the prospective CRANE cohort study of MTX-naïve EORA patients [1, 2]. <h3>Objectives</h3> To identify factors predicting failure to achieve LDA by month 6 in EORA patients starting MTX, and effectiveness and safety of MTX over 5 years in MTX responders and non-responders. <h3>Methods</h3> MTX-naïve patients (mean age 73.8 years, n=163) from the CRANE cohort [2] had started MTX with moderate-to-high disease activity. Maximum dose of MTX was 0.19±0.06 mg/week/kg with folate supplementation. Treatment was adjusted to target LDA. Treatment intensification using biological disease-modifying antirheumatic drugs (bDMARDs) for EULAR-unresponsive patients by month 3 and moderate-high disease activity at month 6 was applied. MTX non-responsiveness was defined as no LDA and/or initiation of bDMARDs by month 6. Primary outcomes were achievement of Simplified disease activity index (SDAI) LDA and discontinuation of MTX due to adverse events (AEs). Secondly outcomes were achievement of remission and Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5, and incidence of serious AEs. <h3>Results</h3> At week 24, 77 (47.2%) patients achieved LDA without bDMARDs (MTX responders), and of the remaining 86 (MTX non-responders), 35 (21.5%) had started bDMARDs by month 6 and 51 (31.3%) had moderate-to-high disease activity on MTX at week 24. At baseline, MTX non-responders had longer disease duration, higher SDAI and HAQ-DI, higher prevalence of erosion score ≥2 (modified total sharp score) and chronic lung disease (CLD), but baseline glucocorticoid use was similar. Multivariable analysis identified CLD as a predictor of MTX non-responsiveness. Regarding long-term outcomes, 14 (18.2%) of the 77 MTX responders and 55 (64%) of the 86 MTX non-responders received intensified treatment with bDMARDs within 5 years. MTX was continued in 65 (94.2%) of the 69 patients at the start of bDMARDs. The Cumulative rate of MTX discontinuation due to AEs was similar in MTX responders and non-responders (34.0% and 33.1%) as was the time to discontinuation of MTX due to AEs. The time to discontinuation of MTX for any reason was also similar. SDAI LDA and HAQ-DI ≤0.5 achievement by year 5 applying the last observation carried forward (LOCF) method was 92.2% and 74.0% respectively for MTX responders and 77.9% and 53.5% for MTX non-responders, respectively (p=0.011 for SDAI LDA and 0.007 for HAQ-DI). SDAI remission at year 5 by LOCF was similar (62.6% and 52.3% in MTX responders-vs-non responders). The time to serious AEs was also similar, as was the cumulative incidence of serious AEs over the 5 years was 32.6% and 44.3% in MTX responders-vs-non-responders. <h3>Conclusion</h3> CLD was a predictive factor of non-achievement of LDA by month 6 in EORA patients starting MTX, and early application of bDMARDs may be adequate for treating EORA with CLD at baseline. The 5-year long-term outcome for MTX responders was excellent, and continuation of MTX was tolerable even in MTX non-responders. Treatment intensification on MTX could be an optimal T2T strategy for EORA. <h3>References</h3> [1] Sugihara T, et al. Rheumatology (Oxford). 2015 May; 54(5):798-807 [2] Sugihara T, et al. Rheumatology (Oxford). 2021;60(9):4252-4261 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Hiroyuki Baba: None declared, Takahiko Sugihara Speakers bureau: Abbvie Japan Co., Ltd., AsahiKASEI Co., Ltd., Astellas Pharma Inc., Ayumi Pharmaceutical, Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi-Tanabe Pharma Co., Ono Pharmaceutical, Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., and UCB Japan Co. Ltd. Tokyo Medical and Dental University received unrestricted research grants for Department of Lifetime Clinical Immunology from Abbvie Japan, Asahi-Kasei, Ayumi Pharmaceutical Corporation, Chugai Pharmaceutical Co., Ltd., CSL Behring K.K., Japan Blood Products Organization, Nippon Kayaku and UCB Japan Co. Ltd., Grant/research support from: AsahiKASEI Co., Ltd., Daiichi Sankyo., Chugai Pharmaceutical Co., Ltd., and Ono Pharmaceutical., Tatsuro Ishizaki: None declared, Manami Nomura: None declared, Tadashi Hosoya: None declared, Mari Kamiya: None declared, Takumi Matsumoto: None declared, Kanae Kubo Speakers bureau: Bristol-Myers Squibb, Chugai Pharmaceutical, Astellas Pharma, Mitsubishi Tanabe Pharma, Daiichi-Sankyo, Boehringer-Ingelheim, AbbVie/Abbott, AsahiKASEI, Pfizer, Paid instructor for: Mitsubishi Tanabe Pharma, AsahiKASEI, Nippon Shinyaku, Chugai Pharmaceutical, Eisai, AbbVie/Abbott, Taisho Pharmaceutical, Grant/research support from: AsahiKASEI, Fumio Hirano: None declared, Nobuyuki Miyasaka: None declared, Masayo Kojima Speakers bureau: AbbVie/Abbott, Astellas, ChugaiPharmaceutical Co., Ltd, Ono Pharmaceutical, Shinsuke Yasuda Speakers bureau: AbbVie/Abbott, AsahiKASEICo., Ltd., Chugai Pharmaceutical Co., Ltd, Ono Pharmaceutical, Tanabe-Mitsubishi Pharmaceutical, Eli Lilly, GlaxoSmithKlein(GSK), Consultant of: Chugai Pharmaceutical Co., Grant/research support from: AbbVie/Abbott, AsahiKASEICo., Ltd., Chugai Pharmaceutical Co., Tanabe-MitsubishiPharmaceutical, Masayoshi Harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi &amp; Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd.